(UroToday.com) The European Society of Medical Oncology (ESMO) 2021 annual meeting’s non-prostate cancer mini-oral session included a presentation by Dr. Lisa Derosa discussing results of the phase 2 GETUG-AFU 26 NIVOREN trial and the impact of antibiotic therapy on outcomes. Previous studies have examined the impact of antibiotics on immune checkpoint inhibitor efficacy across a wide range of tumors, including genitourinary neoplasms. Perturbation of the gut microbiota has been indicated as a putative mechanism to explain this influence. Recently, Dr. Derosa and colleagues published a meta-analysis of 38 studies and 11,959 patients treated with immune checkpoint inhibitors showing that antibiotic therapy 60 days prior to or 42 days after the first administration of anti-PD-1/PD-L1 or anti-CTLA-4 therapy significantly reduced outcomes of immune checkpoint inhibitor therapy.1 At the ESMO 2021 congress, Dr. Derosa and colleagues presented the results of their study assessing the impact of antibiotics in refractory metastatic RCC patients.
The GETUG-AFU 26 NIVOREN phase II trial (NCT 0301335) assessed the activity and safety of nivolumab in metastatic clear cell RCC patients who failed anti-angiogenic regimen. Patients who received antibiotics between 60 days before until 42 days after nivolumab initiation were compared with those who did not. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities were assessed. Multivariate Cox analysis was used to adjust for established risk factors: sex, age, international Metastatic RCC Database Consortium (IMDC) score, number of previous lines, hypoalbuminemia, and brain, bone and liver metastasis.
Among 707 patients included in the study between February 2016 and June 2017, 104 (14.7%) received antibiotics. Characteristics were well balanced except for IMDC score: 12% versus 19% good risk, 49% versus 57% intermediate risk, 39% versus 24% poor risk in antibiotic users versus non-users, respectively. Median OS was 13.0 (95% CI 8.1-19.8; 67/104) months for antibiotic users versus 25.0 (95% CI 22.4-28.4; 284/603) months in non-users (HR 1.77, 95% CI 1.36-2.31):
In multivariate analysis, antibiotics were still associated with worse OS (HR 1.59, 95% CI 1.22-2.09). Median PFS was 2.6 (95%CI 2.4-4.1; 90/104) months in antibiotic users versus 3.8 (95% CI 2.9-4.6; 504/603) months in non-users (HR 1.24, 95% CI 0.99-1.55):
ORR was 15.0% for antibiotic users versus 21.1% for non-users (p=0.176):
Among antibiotic users, there was no complete response and 53 (57.0%) had progressive disease, while 9 (1.5%) and 275 (47.3%) of non-users had complete response and progressive disease, respectively. The incidence of grades 3-5 toxicity leading to a stop in treatment was 26.9% among antibiotic users versus 17.9% of non-users (p=0.031).
Dr. Derosa concluded her presentation with the following take-home messages:
- In this large ‘real world’ setting study of nivolumab in metastatic RCC after failure of at least one TKI, a significant number of patients received antibiotics 60 days before or until 42 days after nivolumab initiation (14.7%)
- Antibiotics severely compromised OS and PFS in metastatic RCC patients treated with nivolumab
- This work provides strong justification for prospective analyses to determine whether microbial infections and antibiotics represent a surrogate for a frail or immunodeficient patient or whether antibiotics directly impair the immune response causing immune checkpoint inhibitor failure
- Consensus guidelines for antibiotic use, as well as diagnostic tools and novel strategies, are needed to decrease antibiotic-induced immune checkpoint inhibitor resistance
Presented by: Lisa Derosa, MD, Medical Oncology Department, Institut Gustave Roussy, Paris, France
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.
References:
- Derosa L, Routy B, Desilets A, et al. Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology? Cancer Discov. 2021 Aug 16 [Epub ahead of print].